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Genome-Wide Association Study of a Heart Failure Related Metabolomic Profile Among African Americans in the Atherosclerosis Risk in Communit...
We sought to identify novel genetic variants that are associated with metabolites previously reported to relate to HF incidence. GWASs of three metabolites identified previously as risk factors for incident HF (pyroglutamine, dihydroxy docosatrienoic acid, and X-11787, being either hydroxy-leucine o...
Identifying rare variants with optimal depth of coverage and cost-effective overlapping pool sequencing.
We proposed an overlapping pool sequencing to screen rare variants with optimal sequencing depth and a corresponding cost model. We formulated a model to compute the optimal depth for sufficient observations of variants in pooled sequencing. Utilizing shifted transversal design algorithm, appropriat...
A shrinkage method for testing the Hardy-Weinberg equilibrium in case-control studies.
We propose a novel shrinkage test for assessing the HWE. The proposed shrinkage test yields higher statistical power than the LRT when the marker is independent of or weakly associated with the disease, and converges to the LRT when the marker is strongly associated with the disease. In addition, th...
A nonparametric test to detect quantitative trait Loci where the phenotypic distribution differs by genotypes.
We introduce in this study a general association test for quantitative trait loci that compare the distributions of phenotypic values by genotypic classes as opposed to most standard tests that compare phenotypic means by genotypic classes. Using simulations we show that in presence of interactions,...
Performance and robustness of penalized and unpenalized methods for genetic prediction of complex human disease.
We present a comprehensive analysis of simulated and real data using lasso and elastic-net penalized support-vector machine models, a mixed-effects linear model, a polygenic score, and unpenalized logistic regression. In simulation, the sparse penalized models achieved lower false-positive rates and...
Extracting actionable information from genome scans.
We propose to extract the available information from a genome scan by accurately estimating the means of univariate statistics. The means are estimated by: (i) computing the sum of squares (SS) of a genome scan's univariate statistics, (ii) using SS to estimate the expected SS for the means (SSM) of...
XM: association testing on the X-chromosome in case-control samples with related individuals.
We propose methods for case-control association testing with X-chromosome markers in samples with related individuals. Our method, XM, appropriately adjusts for both correlation among relatives and male-female allele copy number differences. Features of XM include: (1) it is applicable to and comput...
hTERT cancer risk genotypes are associated with telomere length.
We analyzed 21 polymorphisms, covering 90% of the genetic variance, in the hTERT gene, two genetic variants in hTERC, and relative TL(RTL) at average age 50 and 60 in 959 individuals with repeated blood samples. Mean RTL at age 60 was associated with four genetic variants of the hTERT gene (rs273610...
Smoking and genetic risk variation across populations of European, Asian, and African American ancestry--a meta-analysis of chromosome 15q25...
We demonstrate association between smoking quantity and markers in the chromosome 15q25 region across all three populations, and narrow the region of association. Of the variants tested, only rs16969968 is associated with smoking (P < 0.01) in each of these three populations (odds ratio [OR] = 1.33,...
Next generation analytic tools for large scale genetic epidemiology studies of complex diseases.
Over the past several years, genome-wide association studies (GWAS) have succeeded in identifying hundreds of genetic markers associated with common diseases. However, most of these markers confer relatively small increments of risk and explain only a small proportion of familial clustering. To iden...